variant Creutzfeldt-Jakob disease (vCJD)

Joint statement from the Canadian Hemophilia Society (CHS) and the Association of Hemophilia Clinic Directors of Canada (AHCDC)

vCJD infection reported in a person with hemophilia in UK: FVIII concentrates considered most likely cause

February 19, 2009 - On February 17, the Health Protection Agency in the United Kingdom (UK) reported that a man with hemophilia was found at post mortem examination to have evidence of infection with the agent causing variant Creutzfeldt-Jakob disease (vCJD). The man died of unrelated causes and never showed symptoms of vCJD. As part of an ongoing study, the patient’s spleen was biopsied after his death and evidence of the infectious agent, abnormal prion proteins, was detected. This is the first time that a person with hemophilia has been found to have any evidence of vCJD infection.

vCJD is the human disease caused by infection with an abnormal prion protein. The principal cause is the ingestion of beef infected with Bovine Spongiform Encephalopathy (BSE) or Mad Cow Disease. In the 1980s and 1990s, hundreds of thousands of cattle in the UK died from BSE. The epidemic of BSE affected Europe to a lesser extent. Fewer than 20 cattle have been diagnosed with BSE in North America. No North American has been diagnosed with vCJD from eating North American beef.

In a February 16 statement, after consulting experts in the UK, the World Federation of Hemophilia (WFH) stated,

“This patient had severe hemophilia A, died in his early seventies, and eleven years ago he infused clotting factor concentrate which was later identified as having been contaminated with plasma from a donor who went on to develop vCJD after donation… The patient was a meat-eater, underwent surgical procedures and had received red cell transfusions, all of which are known risk factors for vCJD transmission. However, at this time, investigators believe that the most likely cause of his vCJD infection was the contaminated UK-sourced clotting factor concentrate. A complete medical history is essential for evaluating these risk factors and investigators are still working to complete that part of their study. The judgment that the infection was due to clotting factor concentrates is not final and the WFH will continue to follow this case closely, releasing more information as it becomes available.”

Approximately 200 cases of vCJD have occurred in the world since the mid-1990s, principally in the UK. However, only four cases are blamed on the transfusion of red blood cells from a donor who later developed vCJD. If confirmed, this new case would be the first case of vCJD caused by the infusion of fractioned plasma products such as clotting factor concentrates.SITUATION IN CANADAAccording to manufacturing and medical records, no Canadian has received clotting factor concentrates made with plasma from a donor known to be infected with vCJD.

Approximately 30 Canadians, however, may have used factor XI (factor eleven) concentrates to treat factor XI deficiency made from UK-source plasma in the period 1992-1998. In 2004 Canadian health authorities worked with physicians to notify these patients of the estimated low risk of contracting vCJD from these products.

The Association of Hemophilia Clinic Directors of Canada and the Canadian Hemophilia Society are recommending that physicians notify these 30 patients of this latest development.

The AHCDC and CHS believe that clotting factor concentrates being used in Canada are safe. Virtually all factor VIII and most factor IX concentrates used in Canada are made through recombinant technology and are not plasma-derived and thus do not carry the risk of vCJD. Furthermore, plasma-derived products approved for use in Canada by Health Canada are made with plasma from Canada and U.S., where BSE in cattle is extremely rare. Given the extremely low incidence of vCJD in North America and the manufacturing processes designed to remove prions, these plasma derived products are not considered to be at risk.

Since 1998 plasma from UK donors has not been used in the production of any fractionated plasma products. Since 1999 the Canadian Blood Services and Héma-Québec, as well as blood services in the U.S., have not accepted blood and plasma donations from people who have spent specific periods of time in the UK, France and the rest of Europe.

As a result, the Association of Hemophilia Clinic Directors of Canada recommends that NO changes be made to treatment protocols for people with bleeding disorders.

The Canadian Hemophilia Society and the Association of Hemophilia Clinic Directors of Canada will continue to monitor the situation and provide updates.

For more information, see the World Federation of Hemophilia Web site at www.wfh.org

Statement from the World Federation of Hemophilia

Signs of variant Creutzfeldt-Jakob disease in a patient with hemophilia: FVIII concentrates most likely cause

February 16, 2009 - Health authorities in the United Kingdom have announced that a man with hemophilia was found at post mortem examination to have evidence of infection with the agent causing variant Creutzfeldt-Jakob disease (vCJD). The man died of unrelated causes and never showed symptoms of vCJD. As part of an ongoing study, the patient’s spleen was biopsied after his death and evidence of the infectious agent, abnormal prion proteins, was detected. This is the first time that a person with hemophilia has been found to have any evidence of vCJD infection.

In documents distributed on Monday to hemophilia treaters, the UK Health Protection Agency is stressing that, “This new information does not change the way any patients with bleeding disorders will be treated.” Although this case suggests that those patients exposed to contaminated products in the past may be at risk for vCJD, it does not mean that current plasma-derived products on the market today carry such risk.

Bleeding is still the leading cause of death in people with severe hemophilia, and it is essential to keep these risks in perspective. The WFH continues to view plasma-derived products as an important treatment option for the global bleeding disorders community. In fact, globally, no clotting factor concentrates manufactured today contain UK plasma. In addition, plasma donors who have spent time in the UK are deferred from donating blood or plasma in their own countries. We will continue to engage with health authorities and other stakeholders to remain vigilant concerning the safety of treatment products.

BackgroundThis patient had severe hemophilia A, died in his early seventies, and eleven years ago he infused clotting factor concentrate which was later identified as having been contaminated with plasma from a donor who went on to develop vCJD after donation. In 2004, patients in the UK were notified about the potential risk from UK-sourced products infused between 1980 and 2000 and so may be at elevated risk for vCJD compared to the general population. (WFH TSE Task Force Bulletins on vCJD – 2004) The discovery of abnormal prion proteins in the spleen of this man makes this case similar to the cases of transmission of vCJD through blood transfusion that have been identified in the UK over the past few years. (WFH Statement on Second vCJD Transfusion-Transmission Case)

The patient was a meat-eater, underwent surgical procedures and had received red cell transfusions – all of which are known risk factors for vCJD transmission. However, at this time, investigators believe that the most likely cause of his vCJD infection was the contaminated UK-sourced clotting factor concentrate. A complete medical history is essential for evaluating these risk factors and investigators are still working to complete that part of their study. The judgment that the infection was due to clotting factor concentrates is not final and the WFH will continue to follow this case closely, releasing more information as it becomes available.

Clotting factor concentrates made in the UK from donors who later developed vCJD were exported to several countries in the period 1980-1998. These countries include Brazil, Turkey, Brunei, UAE, India, Jordan, Oman and Singapore. Health authorities in these countries were notified in 2004. In addition, concentrates made from the plasma of UK donors who were never associated with vCJD were exported to an even larger number of countries. The risk from these products is considered very low, but not zero. However, it now seems likely that plasma-derived factor concentrates can transmit vCJD. It is important to remember that this man did not develop vCJD and died from an unrelated cause. It is also important to note that thousands of people with hemophilia in the UK have received factor concentrate that was derived from donors who later developed vCJD. None of these have developed vCJD.

More information will be released in the next few days by the UK Health Protection Agency and the UK Haemophilia Centre Doctors’ Organisation. Check the WFH Web site (www.wfh.org) for links to the latest updates.